title: Potential therapeutic applications of RNA cap analogs.
abstract: Cap analogs are chemically modified derivatives of the unique cap structure present at the 5´ end of all eukaryotic mRNAs and several non-coding RNAs. Until recently, cap analogs have served primarily as tools in the study of RNA metabolism. Continuing advances in our understanding of cap biological functions (including RNA stabilization, pre-mRNA splicing, initiation of mRNA translation, as well as cellular transport of mRNAs and snRNAs) and the consequences of the disruption of these processes - resulting in serious medical disorders - have opened new possibilities for pharmaceutical applications of these compounds. In this review, the medicinal potential of cap analogs in areas, such as cancer treatment (including eIF4E targeting and mRNA-based immunotherapy), spinal muscular atrophy treatment, antiviral therapy and the improvement of the localization of nucleus-targeting drugs, are highlighted. Advances achieved to date, challenges, plausible solutions and prospects for the future development of cap analog-based drug design are described.
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki & Wigury 93, 02-089 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ziemniak
authors.forename: Malwina
authors.initials: M
authors.lastname: Strenkowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Kowalska
authors.forename: Jacek
authors.initials: J
authors.lastname: Jemielity
mesh_terms: D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000627:therapeutic use; D014176:Protein Biosynthesis / Q000187:drug effects; D012314:RNA Cap Analogs / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D012315:RNA Caps / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger; D039601:Eukaryotic Initiation Factor-4A; D004722:Endoribonucleases; C485332:DcpS protein, human